15-41568347-A-T

Position:

• chr15-41568347-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006293.4(TYRO3):​c.1092A>T​(p.Gln364His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: TYRO3 NM_006293.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.16

Genes affected

TYRO3 (HGNC:12446): (TYRO3 protein tyrosine kinase) The gene is part of a 3-member transmembrane receptor kinase receptor family with a processed pseudogene distal on chromosome 15. The encoded protein is activated by the products of the growth arrest-specific gene 6 and protein S genes and is involved in controlling cell survival and proliferation, spermatogenesis, immunoregulation and phagocytosis. The encoded protein has also been identified as a cell entry factor for Ebola and Marburg viruses. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TYRO3	NM_006293.4	c.1092A>T	p.Gln364His	missense_variant	8/19	ENST00000263798.8	NP_006284.2
TYRO3	NM_001330264.2	c.957A>T	p.Gln319His	missense_variant	8/19		NP_001317193.1
TYRO3	XM_017022543.3	c.1092A>T	p.Gln364His	missense_variant	8/19		XP_016878032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TYRO3	ENST00000263798.8	c.1092A>T	p.Gln364His	missense_variant	8/19	1	NM_006293.4	ENSP00000263798	A2
TYRO3	ENST00000559066.5	c.957A>T	p.Gln319His	missense_variant	8/19	5		ENSP00000454050	P4
TYRO3	ENST00000559815.1	c.291A>T	p.Gln97His	missense_variant, NMD_transcript_variant	2/4	5		ENSP00000453835

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 21, 2023

The c.1092A>T (p.Q364H) alteration is located in exon 8 (coding exon 8) of the TYRO3 gene. This alteration results from a A to T substitution at nucleotide position 1092, causing the glutamine (Q) at amino acid position 364 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Uncertain	0.055	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.022	T;T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.85	T;T
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.48	T;T
MetaSVM	Benign	-0.57	T
MutationAssessor	Uncertain	2.2	.;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.25
Sift	Benign	0.18	T;T
Sift4G	Benign	0.45	T;T
Polyphen		1.0	.;D
Vest4		0.61
MutPred		0.51		.;Gain of ubiquitination at K359 (P = 0.1162);
MVP		0.44
MPC		0.66
ClinPred		0.80	D
GERP RS		4.0
Varity_R		0.23
gMVP		0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-41860545;